Significance: HIV infected drug users have greater difficulty adhering to HAART compared to non-drug users. As sustained adherence is critical to reducing HIV related morbidity and mortality, innovative and potentially sustainable treatment strategies that can optimize the durability of adherence enhancing interventions among drug users are urgently needed. Increasingly, interventions using communication technologies (e.g.,smartphones) to assess and enhance treatments are being used for a variety of somatic, mental health and substance abuse conditions. Innovation/Approach: Consistent with NIDA's mission to develop novel technological based interventions to promote adherence to HAART the goal of this R-34 application is to use the stage model of behavioral therapy research to adapt, further develop, complete preliminary usability and pilot testing of a smart phone based intervention called HEART (Helping Enhance Adherence to Retroviral therapy using Technology) to HAART, to enhance, promote, and improve long-term adherence to HAART among HIV infected drug users in the non- methadone maintenance setting. Informed by Wagner's Chronic Care Model, the HEART to HAART intervention is designed to enhance ongoing adherence counseling by providing (1) real time information about medication adherence (using Wisepill device);(2) periodic assessment of medication side effects, depressive symptoms and drug use frequency (as these are linked to poor adherence among drug users) using ecological momentary assessment and (3) tailored education, recommendation and encouragement based on assessments. The participant (using their phone) and their adherence team (using a clinician interface) can jointly track real time changes in adherence increasing the potential for shared decision-making. This proposal has three aims consistent with stage 1A and 1B of the stage of behavioral therapy research. Aims 1 and 2 seek to adapt and further develop (Stage 1A) HEART to HAART. Aims 1 and 2 will use an iterative user-centered design that allows end users of a system to influence how a design takes shape to increase the ease with which a system can be learned and used. Aim 3 will test the preliminary efficacy (Stage 1B) of the finalized form of HEART to HAART. In aim 3, a total of 50 HIV infected, drug users receiving adherence counseling at an urban, outpatient HIV clinic will be randomly assigned to receive either HEART to HAART versus usual care with the addition of a smart phone control. The intervention will last 24 weeks and the primary outcome will be change in adherence as measured by unannounced telephone based random pill counts. Changes in biological outcomes including HIV viral load and CD4 count will also be evaluated. Implication: If shown to be acceptable and efficacious HEART to HAART may introduce a fundamentally new method of HAART medication self-management and provide a tailored, potentially sustainable and less cost intensive intervention that can increase adherence among HIV infected drug users over the long term. PUBLIC HEALTH RELEVANCE: HIV infected drug users have greater difficulty adhering to highly active antiretroviral therapy compared to non-drug users. As sustained adherence to highly active antiretroviral therapy is critical to reducing HIV related morbidity, mortality, and reducing the spread of HIV, innovative and potentially sustainable treatment strategies that can optimize the durability of adherence enhancing interventions among drug users is urgently needed. The goal of this R-34 application is to further develop and pilot test a smartphone based intervention called HEART (Helping Enhance Adherence to Retroviral therapy using Technology) to HAART, to enhance adherence to HAART among HIV infected drug users.